We propose a program of epidemiologic research using statistical monitoring of a large data set for unusual occurrences of rare tumors that offer some epidemiologic clues to etiology. We will verify and then do a field investigation of selected unusual occurrences to develop etiologic hypotheses. Hypotheses developed during the field investigation will be tested using a case-control study. As such, this proposal includes three integrated parts. First, we propose to develop the above mentioned data monitoring protocol to be used with the SEER data in the San Francisco (S.F.) Bay Area. Second, we propose a preliminary investigation of a cluster (six cases in a 20-block radius) of Ewing's sarcoma, a rare bone tumor that would have been revealed by the data-monitoring system had it been underway. Though this unusual occurrence came to our attention by a serendipitous means, it offers an opportunity to use the field procedures required to verify unusual occurrences and to develop realistic etiologic hypotheses. We will then do a study of Ewing's sarcoma with 35 cases and 140 controls to test the hypotheses generated during the field investigation. Third, we propose a case-control test of an etiologic hypothesis with another rare tumor, squamous-cell cancer of the anus and rectum (0.2% of all malignancies in the U.S.). This rare tumor, through no organized mechanism, has been verified to occur with at least a 4-fold excess in single males, have a higher rate in S.F. County than in surrounding counties and appears to occur at higher rates in homosexual males, especially those with a history of anal papillomata. This etiologic hypothesis is developed sufficiently to test and S.F. has the appropriate population. We propose to interview 170 cases and 340 controls in this population-based study in the S.F. SEER region to test hypotheses relating anal and rectal squamous-cell carcinoma to anal intercourse, herpes, condyloma, other anal or rectal problems and treatments for these conditions. Both tumor sites represent rare tumors worthy of investigation. This project proposes to use the two types of investigations required to establish and test hypotheses and to test all the administrative and scientific steps in rare tumor investigation.